Heparan sulfate proteoglycans are ubiquitous components of the pericellular matrix of adherent cells. They are presumed to be involved in processes that are essential to the orderly development and normal function of tissues, such as cell adhesion, changes in cell shape, cell growth and extracellular matrix assembly. While some pericellular HS proteoglycans appear to be part of the extracellular matrix proper, other forms display properties generally ascribed to integral membrane proteins, suggesting structural heterogeneity. Whether this structural heterogeneity has relevance for the diversity of the functions that have been ascribed to HS proteoglycans is unknown. The present proposal aims at (i) establishing whether structural heterogeneity exists amongst HS proteoglycans produced by normal human embryonic lung fibroblasts; (ii) at assessing the basis for their possible heterogeneity and (iii) at developing probes that would allow to relate the structural features of these molecules to their function. Specifically, it is proposed to map and to compare the core protein structure of membrane-associated and secreted HS proteoglycans by chemical means and by monoclonal antibody probes, and to try to define functional domains in the peptide moiety of these molecules. This information should allow to test the hypothesis that HS proteoglycans of normal human lung fibroblasts are initially synthesized as integral membrane proteins and that they are secreted by extracellular proteolytic processing of the anchoring core protein. Controlled proteolytic processing of cell-surface HS proteoglycans could indeed be a mechanism by which cells regulate the deposition of these molecules and their associated ligands in the extracellular matrix. The obtained probes should allow to better define the role of HS proteoglycan in lung matrix assembly. Ultimately, they may allow us to assess whether and to what extent the HS proteoglycans of the lung interstitial tissue are the targets of the processes that lead to the unappropriate matrix assembly of chronic lung disease.